T cell based immunotherapy is highly effective for cancer treatment as evidenced by recent reports with chimeric antigen receptors, bispecific antibodies, and checkpoint blockade antibodies. Both chimeric antigen receptors and bispecific antibodies have relied on antibody-based targeting of surface antigens. T cell receptor (TCR)-based approaches, however, have been slower in their development due in part to insufficient clonal frequency or clonal deletion of tumor-specific T cells and dwarfed by the rapid advances in antibody libraries and platform technologies. Unfortunately, clinically approved therapeutic monoclonal antibodies recognize structures of cell surface proteins. Moreover, antibody-based targetable antigens are limited in number. Of the candidates on the National Cancer Institute (NCI) cancer antigen priority list, the majority are found in the cytoplasmic compartment. Development of antibody agents targeting such candidates remains a challenge.